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. 2019 Aug 3;20(15):3791. doi: 10.3390/ijms20153791

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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ROS regulation of Keap1/Nrf2/p62 signaling and its impact on autophagy. (A) Under normal basal conditions, Keap1 regulates Nrf2 and keeps its level low by ubiquitination and proteosomal degradation. (B) P62 has a binding site for Keap 1 and promotes autophagic degradation of Keap1, liberating Nrf2 and enabling Nrf2 to translocate to the nucleus to transactivate target genes to protect against oxidative stress and upregulate autophagy. (C) Under oxidative stress conditions, Keap1 is oxidized by ROS-mediated oxidation of cysteine thiols in the cysteine-rich Keap1-Cullin3-based ubiquitin ligase complex, which dissociates Nrf2 from Keap1 and enables Nrf2 to translocate to the nucleus to transactivate target genes, including antioxidant and autophagy genes.